<p>This prospective observational study investigated the differential modulation of metabolic parameters by modified traditional Japanese dietary therapy for diabetes (MJDD) and SGLT-2 inhibitor canagliflozin in treatment-naïve patients with T2DM. Particular emphasis was placed on adipose tissue insulin resistance (adipo-IR). Newly diagnosed, drug-naïve T2DM patients were treated with either MJDD (n = 53) or canagliflozin (n = 55) for 3&#xa0;months. Key metabolic indices-including BMI, FBG, HbA1c, insulin, FFA, HOMA-R, HOMA-B, and adipo-IR-were measured. Correlations between weight change (ΔBMI) and metabolic responses were analyzed. Subgroup comparisons were performed based on median BMI change. Both strategies improved glycemic control and insulin resistance, as reflected by reductions in FBG, HbA1c, insulin, and HOMA-R, along with increased HOMA-B. Notably, reductions in FFA and adipo-IR were observed exclusively with MJDD. In the MJDD group, weight loss significantly correlated with improvements in FBG, insulin, HOMA-R, and adipo-IR, whereas no such associations were noted with canagliflozin. Subgroup and regression analyses indicated that effects of MJDD on adipo-IR were weight-dependent, with baseline adipo-IR being the strongest predictor of improvement. In contrast, canagliflozin improved glycemic markers largely independent of body weight change. Collectively, MJDD and canagliflozin both modulate metabolic dysfunction in early T2DM, but through distinct mechanistic pathways. MJDD exerts weight-dependent metabolic benefits, particularly improving adipo-IR and FFA levels. In contrast, canagliflozin improves glycemic control and systemic insulin sensitivity independently of weight loss, highlighting potential tissue-specific or non-insulin-mediated mechanisms. To our knowledge, this is the first report to demonstrate that dietary intervention can directly regulate adipose tissue insulin resistance.</p>